The present invention relates to a single or multi-well filtration device suitable for the concentration or assay of biological and biochemical materials. The present invention more particularly relates to a single or multi-well filtration device having the filtration media sealed to the underdrain of the device.
Test plates having one or more individual wells or reaction chambers are common laboratory tools. Such devices are employed for a wide variety of purposes and assays, see U.S. Pat. No. 4,902,481. Single welled devices are also well known, see U.S. Pat. Nos. 3,483,768, 4,632,761 and 4,722,792.
The plate filtration devices include two plates, the upper plate, commonly referred to as the well plate and a lower plate, commonly referred to as the underdrain. The well plate contains one or more individual wells that are open at one end and have a filtration membrane sealed across the opposite end. The underdrain is provided with a second set of individual well(s), which register with the wells of the well plate. Each of the wells in the underdrain have an open end and a second end which contains a small opening having a spout which opening and spout are designed to receive liquid which passes through the filtration membrane of the upper plate. The size of the opening and the spout are controlled so that liquid is retained in the well plate above the membrane under normal atmospheric conditions due to surface tension forces but passes through the membrane and the opening and spout when a pressure differential is applied across the membrane.
The filtration media has been secured to the lower portion of the well plate in several ways. In one method, a sheet of filtration membrane is stretch across the bottom of the well plate and adhered to each of the individual well or wells. In a second method, individual membrane pieces are cut and placed within the interior of the well where either friction or an undercut is used to maintain the position of the membrane in the well. In a third common method, the individual pieces are adhered to the bottom portion of the individual wells of the well plate.
The first method has problems in that liquid that passes through the membrane can travel laterally between wells and contaminate adjacent wells. The second method relies upon proper placement and maintenance of that placement in the well over time. Vibration, rough handling and other factors can displace the membrane causing loss of the sample or at least a portion of the sample or liquid within the sample. Additionally, it fails to form an integral seal such that liquid may bypass the filter altogether resulting in loss of product and contamination of the filtrate. The third method has been the preferred and most commonly used method as it ensures that there is no cross talk or contamination between the wells and there is a true seal of the membrane to the well plate so as to prevent leakage.
In these devices, the membrane has been limited to microporous membrane or a glass fiber depth filter or other coarse filtration media. This is due to the nature of the membrane and its ability to be sealed to the bottom of the well in the well plate. Other membranes, in particular ultrafiltration (UF) membranes are mentioned as being of possible use, however they have not been successfully sealed within the well plate. This is due to the structure and composition of the UF membranes. These membranes are relatively thin and fragile. Therefore these membranes are typically cast upon a support structure such as a non-woven porous sheet or a microporous membrane. The UF membrane itself is a relatively thin, dense material which is extremely sensitive to any type of mechanical or chemical bonding method.
What is desired is a plate system which allows for the use of membranes other than microporous membranes and which contains all of the advantages of the prior plates, namely avoiding lateral flow and contamination between the wells and the use of multiple wells in the same device. The present invention provides such a device.
The present invention provides an improved single or multi-well filtration apparatus that permits the use of membranes other than microporous membranes, in particular UF membranes, nanofiltration membranes and reverse osmosis membranes. Additionally, the present invention provides such a device that is capable of having liquid removed from each well by filtration with a vacuum or under pressure including by centrifugal forces. The filtrate from each well is recovered separately from the filtrate in adjacent wells. Thus, this apparatus permits the recovery and/or analysis of the retentate and/or filtrate without cross contamination between the adjacent wells.
The present invention has a well plate having both ends open and an underdrain that has one end (the lower end) essentially closed except for a small opening and spout. The other end of the underdrain has a filtration membrane sealed across the well such that any liquid will be retained in the well of the well plate until either a vacuum or positive pressure is applied to filter the liquid through the membrane. The membrane is sealed to the well of the underdrain by any conventional method such as heat bonding, ultrasonic bonding, vibrational bonding, friction bonding, adhesive bonding, solvent bonding or overmolding. It is preferred that the membrane be sealed to the underdrain by heat bonding.
It is a preferred object of the present invention to provide a filtration device having an underdrain portion having one or more individual drain compartments, each of said one or more compartments having a drain opening and a drain compartment wall located adjacent the outer periphery of each compartment; one or more filter components located din in one or more of the drain compartments contained in the underdrain portion, each of said filter components being attached to the underdrain portion in a manner to form in integral seal between the periphery of the filter component and a drain compartment of the underdrain portion; and a well plate having one or more individual wells, said plurality of wells being arranged in number and location so as to register with the underdrain portion.
It is another preferred object of the present invention to provide a multiple well device having an underdrain portion having a plurality of individual drain compartments, each of said compartments having a drain opening formed in the lower portion of the compartment and a drain compartment wall located adjacent the outer periphery of the compartment; a plurality of filter components contained in at least a portion of the compartments of the underdrain portion, each of said filter components being attached to the underdrain portion so as to form an integral seal between the periphery of the filter component and the compartment of the underdrain portion; and a well plate having a plurality of individual wells, said plurality of wells being arranged in a number and location so as to register with the underdrain portion when said well plate is placed onto of the underdrain portion.
It is a further preferred object of the present invention to provide a method of forming a multiple well filtration device by forming an underdrain portion, said underdrain portion having a plurality of individual drain compartments, said compartments having a drain opening, a filter support surrounding said drain opening and a drain compartment wall located adjacent the outer periphery of the filter support; placing a filter component in each of the drain compartments contained in the underdrain portion, attaching the filter component in each of said drain compartments at the periphery of the filter component to the drain compartment in a manner to form in integral seal between the periphery of the filter component and a drain compartment of the underdrain portion; forming a well plate having a plurality of individual wells, said plurality of wells being equal in number and location with the number and location of the plurality of drain compartments in the underdrain portion; and securing the well plate to the underdrain portion so as to form a plurality of sealed well filtration devices, each having a well, a drain and a filter sealed in between.
It is a further preferred object of the present invention to provide a filtration apparatus formed of a first plate having at least one first well, each of said at least one first wells having a first open end and a second open end and an outside peripheral surface, a second plate having at least one second well having a first open end, a first closed end, said closed end having a hole extending through the closed end thickness and an inside peripheral surface, said second plate being secured to said first plate so as to form a continuous well between the top of the first plate and the first closed end of the second plate, a filter positioned between said second end of said first plate and said first closed end of said second plate and an open spout having an open end, said spout being in fluid communication with said hole.
These and other embodiments and objects of the present invention will be made clear from the following description and claims.